Modulation of host immune responses stimulated by Salmonella vaccine carrier strains by using different promoters to drive the expression of the recombinant antigen

We evaluated whether immune responses stimulated by Salmonella vaccine carr iers can be modulated by using different promoters to drive antigen express ion. Mice were orally immunized with strains transfected with plasmids carr ying beta-galactosidase (beta-gal) under the control of either a constituti ve or an in vivo-activated promoter. While beta-gal-reactive IgG1, IgG2a, I gG2b and IgG3 were detected in sera of mice immunized with Salmonella expre ssing constitutively beta-gal, higher titers dominated by IgG2a and IgG2b w ere detected in sera when the in vivo-activated promoter was used. beta-gal -specific proliferative responses of spleen derived CD4(+) T lymphocytes we re similar in both groups. However, CD4(+) T lymphocytes from mice immunize d with the constitutive promoter secreted IL-4, IL-5, IL-6, IL-10 and IFN-g amma (Th1/Th2 pattern), whereas CD4(+) cells mainly secreted IFN-gamma (Th1 pattern) when the second construct was used. The spleens of all immunized mice contained beta-gal-reactive CD8(+) CTL precursors. The vaccine prototy pes were tested for their capacity to control seeding and/or development wi thin the lung of an intravenously delivered aggressive fibrosarcoma transfe cted with beta-gal. Reduced metastasis and significantly increased mean sur vival times were observed in all vaccinated mice. However, protection was i mproved when the carrier expressed beta-gal upon infection (80% Versus 50% survival, p < 0.05).